can nanotechnology improve cancer diagnosis through mirna detection

miRNAs are key regulators of gene expression, and alterations in their expression levels correlate with the onset and progression of cancer. Although miRNAs have been proposed as biomarkers for cancer diagnosis, their application in routine clinical praxis is yet to come. Current quantification strategies have limitation, and there is a great interest in developing innovative ones. Since a few years, nanotechnology-based approaches for miRNA quantification are emerging at fast pace but there is urgent need to go beyond the proof-of-concept stage. Nanotechnology will have a strong impact on cancer diagnosis through miRNA detection only if it is demonstrated that the newly developed approaches are indeed working on 'real-world' samples under standardized conditions

Gold-Nanoparticle-Based Colorimetric Discrimination of Cancer-Related Point Mutations with Picomolar Sensitivity

Point mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) gene are being increasingly recognized as important diagnostic and prognostic markers in cancer. In this work, we describe a rapid and low-cost method for the naked-eye detection of cancer-related point mutations in KRAS based on gold nanoparticles. This simple colorimetric assay is sensitive (limit of detection in the low picomolar range), instrument-free, and employs nonstringent room temperature conditions due to a combination of DNA-conjugated gold nanoparticles, a probe design which exploits cooperative hybridization for increased binding affinity, and signal enhancement on the surface of magnetic beads. Additionally, the scheme is suitable for point-of-care applications, as it combines naked-eye detection, small sample volumes, and isothermal (PCR-free) amplification

InP/ZnS as a safer alternative to CdSe/ZnS core/shell quantum dots: in vitro and in vivo toxicity assessment

We show that water soluble InP/ZnS core/shell QDs are a safer alternative to CdSe/ZnS QDs for biological applications, by comparing their toxicity in vitro (cell culture) and in vivo (animal model Drosophila). By choosing QDs with comparable physical and chemical properties, we find that cellular uptake and localization are practically identical for these two nanomaterials. Toxicity of CdSe/ZnS QDs appears to be related to the release of poisonous Cd(2+) ions and indeed we show that there is leaching of Cd(2+) ions from the particle core despite the two-layer ZnS shell. Since an almost identical amount of In(III) ions is observed to leach from the core of InP/ZnS QDs, their very low toxicity as revealed in this study hints at a much lower intrinsic toxicity of indium compared to cadmium

Reversible site-specific tagging of enzymatically synthesized RNAs using aldehyde–hydrazine chemistry and protease-cleavable linkers

The investigation of RNA structure, dynamics and biological function often requires the site-specific incorporation of non-natural moieties. Here we describe the functionalization of RNA transcripts by aldehyde–hydrazine chemistry using a simple initiator nucleotide that carries an acetal-protected aldehyde function. This initiator nucleotide was efficiently incorporated into RNA, and the modified RNAs were quantitatively coupled to a peptide derivative displaying a hydrazine moiety at one end, a biotin tag at the other, and a trypsin-cleavable sequence in between. RNA conjugates could be easily isolated by affinity chromatography on streptavidin agarose and quantitatively cleaved off the support by trypsin treatment without detectable RNA degradation. The strategy described here may allow the incorporation of various new features into enzymatically synthesized RNA under mild conditions

Reply to Comment on Conopeptide-Functionalized Nanoparticles Selectively Antagonize Extrasynaptic N-Methyl-d-aspartate Receptors and Protect Hippocampal Neurons from Excitotoxicity In Vitro

In this manuscript, we provide precise answers to the concerns expressed by Molokanova et al. in their comment. In our reply, we highlight that there is indeed substantial agreement between our study and the one reported in Nano Letters by the Molokanova’s group.1 We believe this is a very important aspect because it proves the validity of the chosen approach, i.e. PEGylated AuNPs carrying NMDAR antagonists and with an overall dimension large enough to prevent their diffusion into the synapse can exclusively antagonize extrasynaptic NMDAR-mediated currents and are thereby neuroprotective

Reversible site-specific tagging of enzymatically synthesized RNAs using aldehyde–hydrazine chemistry and protease-cleavable linkers

The investigation of RNA structure, dynamics and biological function often requires the site-specific incorporation of non-natural moieties. Here we describe the functionalization of RNA transcripts by aldehyde–hydrazine chemistry using a simple initiator nucleotide that carries an acetal-protected aldehyde function. This initiator nucleotide was efficiently incorporated into RNA, and the modified RNAs were quantitatively coupled to a peptide derivative displaying a hydrazine moiety at one end, a biotin tag at the other, and a trypsin-cleavable sequence in between. RNA conjugates could be easily isolated by affinity chromatography on streptavidin agarose and quantitatively cleaved off the support by trypsin treatment without detectable RNA degradation. The strategy described here may allow the incorporation of various new features into enzymatically synthesized RNA under mild conditions

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses

Mucin-1 (MUC1) glycopeptides are exceptional candidates for potential cancer vaccines. However, their autoantigenic nature often results in a weak immune response. To overcome this drawback, we carefully engineered synthetic antigens with precise chemical modifications. To be effective and stimulate an anti-MUC1 response, artificial antigens must mimic the conformational dynamics of natural antigens in solution and have an equivalent or higher binding affinity to anti-MUC1 antibodies than their natural counterparts. As a proof of concept, we have developed a glycopeptide that contains noncanonical amino acid (2S,3R)-3-hydroxynorvaline. The unnatural antigen fulfills these two properties and effectively mimics the threonine-derived antigen. On the one hand, conformational analysis in water shows that this surrogate explores a landscape similar to that of the natural variant. On the other hand, the presence of an additional methylene group in the side chain of this analog compared to the threonine residue enhances a CH/π interaction in the antigen/antibody complex. Despite an enthalpy–entropy balance, this synthetic glycopeptide has a binding affinity slightly higher than that of its natural counterpart. When conjugated with gold nanoparticles, the vaccine candidate stimulates the formation of specific anti-MUC1 IgG antibodies in mice and shows efficacy comparable to that of the natural derivative. The antibodies also exhibit cross-reactivity to selectively target, for example, human breast cancer cells. This investigation relied on numerous analytical (e.g., NMR spectroscopy and X-ray crystallography) and biophysical techniques and molecular dynamics simulations to characterize the antigen–antibody interactions. This workflow streamlines the synthetic process, saves time, and reduces the need for extensive, animal-intensive immunization procedures. These advances underscore the promise of structure-based rational design in the advance of cancer vaccine development

Structure-Guided Approach for the Development of MUC1-Glycopeptide-Based Cancer Vaccines with Predictable Responses

Mucin-1(MUC1)glycopeptidesareexceptionalcandidatesforpotentialcancervaccines.However,theirautoantigenicnatureoftenresultsinaweakimmuneresponse.Toovercomethisdrawback,wecarefullyengineeredsyntheticantigenswithprecisechemicalmodifications.Tobeeffectiveandstimulateananti-MUC1response,artificialantigensmustmimictheconforma-tionaldynamicsofnaturalantigensinsolutionandhaveanequivalentorhigherbindingaffinitytoanti-MUC1antibodiesthantheirnaturalcounterparts.Asa proofofconcept,wehavedevelopeda glycopeptidethatcontainsnoncanonicalaminoacid(2S,3R)-3-hydroxynorvaline.Theunnaturalantigenfulfillsthesetwopropertiesandeffectivelymimicsthethreonine-derivedantigen.Ontheonehand,conformationalanalysisinwatershowsthatthissurrogateexploresalandscapesimilartothatofthenaturalvariant.Ontheotherhand,thepresenceofanadditionalmethylenegroupinthesidechainofthisanalogcomparedtothethreonineresidueenhancesa CH/interactionintheantigen/antibodycomplex.Despiteanenthalpyentropybalance,thissyntheticglycopeptidehasabindingaffinityslightlyhigherthanthatofitsnaturalcounterpart.Whenconjugatedwithgoldnanoparticles,thevaccinecandidatestimulatestheformationofspecificanti-MUC1IgGantibodiesinmiceandshowsefficacycomparabletothatofthenaturalderivative.Theantibodiesalsoexhibitcross-reactivitytoselectivelytarget,forexample,humanbreastcancercells.Thisinvestigationreliedonnumerousanalytical(e.g.,NMRspectroscopyandX-raycrystallography)andbiophysicaltechniquesandmoleculardynamicssimulationstocharacterizetheantigenantibodyinteractions.Thisworkflowstreamlinesthesyntheticprocess,savestime,andreducestheneedforextensive,animal-intensiveimmunizationprocedures.Theseadvancesunderscorethepromiseofstructure-basedrationaldesignintheadvanceofcance

Synthetic self-assembled models with biomimetic functions

Self-assembly can be considered a powerful tool in the hand of chemists for the understanding, modeling and mimicking of biological systems. The possibility of reproducing biological functions in synthetic systems obtained by self-assembly is envisioned as a modest but very important step towards the understanding of the mystery of life and its emergence on Earth